Anti-aging products that treat wrinkling, creasing and furrowing of the skin are in high demand among consumers who want to keep their skin youthful and smooth. Treating expression lines of the face by applying topical cosmetics that are effective and non-invasive attracts the interests of both the consumer and the researcher.
Expression lines, a distinct type of wrinkle that occurs on the facial skin, are a problem for people who want to maintain a youthful appearance. The formation of expression lines is related to the facial expression muscles, whose activities during the actions of smiling, squinting, and frowning place more tension on the muscles and greater stress on the overlying skin. The facial muscle contraction is controlled by certain neurotransmitter, such as acetylcholine, the inhibition of whose release is the basis of some cosmetic products directed against expression wrinkles.
For example, Botulinum toxin A (BOTOX®) is one of the commonly used molecules that inhibit acetylcholine secretion and reduce facial expression wrinkles. Its mechanism hinges on the cleavage of a neuronal protein SNAP-25, whose presence is essential to the formation of a protein complex (SNARE complex) which directs and controls the release of acetylcholine accumulated in vesicles. The therapeutic and cosmetic treatment with BOTOX® is expensive, requires repeated injections, and may trigger immune reactions in patients/consumers.
U.S. Pat. No. 6,169,074 to Montal, et al. discloses combinations of peptides that interfere with the SNARE complex within the synaptic gap on the neuromuscular junction. U.S. Pat. No. 6,866,856 to Lu, et al. describes limonoids (alkaloid extracts of citrus fruits) that inhibit acetylcholine release at the neuromuscular junction of skeletal muscle. U.S. Pat. No. 7,566,464 to Belfer teaches a skin care composition that improves the appearance of expression lines of the human face comprising an extract of Acmella oleracea which rapidly relaxes the contractile muscle elements and suppresses the action of the expressive facial muscle based on the perceived synergy of strengthening the dermis and inhibiting the muscle tissues related to expression lines.
Furthermore, U.S. Pat. No. 7,015,192 to Blanes, et al. discovers that peptides derived from the N-terminal end of protein SNAP-25 inhibit acetylcholine release within the SNAR complex. The principle molecule, acetyl hexapeptide-3 (ARGIRELINE®) is claimed to compete with the efficacy of Botulinum toxin but without the risks, the injections and the high cost.
The rate and depth of skin penetration of topical cosmetics agents affects the dose of the administered agents. Peptides existing in zwitterion forms present a problem for topical applications and decrease their efficacy. Modification of the peptide structure to increase the permeability of the resulting derivatives into the target cells is one strategy to solve this problem.
Thus, there is a need in the art to discover peptide-based compounds which predominantly exist in non-charged forms when applied on the skin and inhibit neurotransmitter release and muscle contraction as a treatment for wrinkles.